Abstracts
Résumé
La tyrosinémie héréditaire de type 1 est la maladie la plus sévère de la voie du catabolisme de la tyrosine et est due à une perte d’activité de la fumarylacétoacétate hydrolase. Les patients souffrent principalement d’atteinte hépatique conduisant le plus souvent au cancer du foie. À partir des données récentes sur les sites d’action des métabolites toxiques, un nouveau modèle permettant d’expliquer l’étiopathogénie de la tyrosinémie héréditaire de type 1 - et, notamment, le taux élevé de cancer du foie observé - peut être proposé.
Summary
Hereditary tyrosinemia type 1 (HT1) is the most severe metabolic disease associated with tyrosine catabolism. An accumulation of toxic metabolites seems responsible for the pathology of HT1. The metabolite fumarylacetoacetate, accumulating due to a deficiency in fumarylacetoacetate hydrolase, displays apoptogenic, mutagenic, aneugenic and mitogenic activities. These effects may underlie the tumorigenic phenomenon observed in HT1. Fumarylacetoacetate in addition to causing disturbances in Ca2+ homeostasis, may induce endoplasmic reticulum stress.
Appendices
Références
- 1. Mitchell GA, Grompe M, Lambert M, Tanguay RM. Hypertyrosinemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited diseases, 8e ed. New York: McGraw-Hill, 2001: 1777-805.
- 2. Lindsted S, Holme E, Lock EA, Hialmarson O, Strandvik B. Treatment of hereditary tyrosinaemia type 1 by inhibition of 4-hydroxyphenylpyruvate dioxygenase. Lancet 1992; 340: 813-7.
- 3. De Braekeleer M, Larochelle J. Genetic epidemiology of hereditary tyrosinemia in Quebec and in Saguenay-Lac-St-Jean. Am J Hum Genet 1990; 47: 302-7.
- 4. Poudrier J, St-Louis M, Lettre F, et al. Frequency of the IVS12+5g: a splice mutation of the fumarylacetoacetate hydrolase gene in carriers of hereditary tyrosinemia in the French Canadian population of Saguenay-Lac-St-Jean. Prenat Diagn 1996; 16: 59-64.
- 5. St-Louis M, Tanguay RM. Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type 1: overview. Hum Mutat 1997; 9: 291-9.
- 6. Arranz JA, Pinol F, Kozak L, et al. Splicing mutations, mainly IVS6-1(g>t), account for 70 % of fumarylacetoacetate hydrolase (FAH) gene alterations, including 7 novel mutations, in a survey of 29 tyrosinemia type I patients. Hum Mutat 2002; 20: 180-8.
- 7. Poudrier J, Lettre F, Scriver CR, Larochelle J, Tanguay RM. Different clinical forms of hereditary tyrosinemia (type 1) in patients with identical genotypes. Mol Genet Metab 1998; 64: 119-25.
- 8. Kvittingen EA, Rootwelt H, Brandtzaeg P, Bergan A, Berger R. Hereditary tyrosinemia type 1. Self-induced correction of the fumarylacetoacetase defect. J Clin Invest 1993; 91: 1816-21.
- 9. Kvittingen EA, Rootwelt H, Berger R, Brandtzaeg P. Self-induced correction of the genetic defect in tyrosinemia type 1. J Clin Invest 1994; 94: 1657-61.
- 10. Overturf K, Al-Dhalimy M, Tanguay RM, et al. Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinemia type I. Nat Genet 1996; 12: 266-73.
- 11. Jorquera R, Tanguay RM. Cyclin B-dependent kinase and caspase-1 activation precedes mitochondrial dysfunction in fumarylacetoacetate-induced apoptosis. Faseb J 1999; 13: 2284-98.
- 12. Kubo S, Sun M, Miyahara M, et al. Hepatocyte injury in tyrosinemia type 1 is induced by fumarylacetoacetate and is inhibited by caspase inhibitors. Proc Natl Acad Sci USA 1998; 95: 9552-7.
- 13. Weinberg AG, Mize CE, Worthen HG. The occurrence of hepatoma in the chronic form of hereditary tyrosinemia. J Pediatr 1976; 88: 434-8.
- 14. Tanguay RM, Jorquera R, Poudrier J, St-Louis M. Tyrosine and its catabolites: From disease to cancer. Acta Biochim Pol 1996; 43: 209-16.
- 15. Jorquera R, Tanguay RM. The mutagenicity of the tyrosine metabolite, fumarylacetoacetate, is enhanced by glutathione depletion. Biochem Biophys Res Commun 1997; 232: 42-8.
- 16. Jorquera R, Tanguay RM. Fumarylacetoacetate, the metabolite accumulating in hereditary tyrosinemia, activates the ERK pathway and induces mitotic abnormalities and genomic instability. Hum Mol Genet 2001; 10: 1741-52.
- 17. Gilbert-Barness E, Barness LA, Meisner LF. Chromosomal instability in hereditary tyrosinemia type1. Pediatr Pathol 1990; 10: 243-52.
- 18. Prieto-Alamo MJ, Laval F. Deficient DNA-ligase activity in the metabolic disease tyrosinemia type I. Proc Natl Acad Sci USA 1998; 95: 12614-8.
- 19. Kelsey G, Ruppert S, Beermann F, Grund C, Tanguay RM, Schutz G. Rescue of mice homozygous for lethal albino deletions: Implications for an animal model for the human liver disease tyrosinemia type I. Genes Dev 1993; 7: 2285-97.
- 20. Spear E, Ng DT. The unfolded protein response: No longer just a special teams player. Traffic 2001; 2: 515-23.
- 21. Yoneda T, Urano F, Ron D. Transmission of proteotoxicity across cellular compartments. Genes Dev 2002; 16: 1307-13.
- 22. Kaufman RJ. Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 1999; 13: 1211-33.
- 23. Al-Dhalimy M, Overturf K, Finegold M, Grompe M. Long-term therapy with NTBC and tyrosine-restricted diet in a murine model of hereditary tyrosinemia type I. Mol Genet Metab 2002; 75: 38-45.